title: HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients.
abstract: Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, WA, USA. danielle.zerr@seattlechildrens.org
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Zerr
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Fann
authors.forename: David
authors.initials: D
authors.lastname: Breiger
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Adler
authors.forename: Hu
authors.initials: H
authors.lastname: Xie
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000453:epidemiology / Q000821:virology*; D003693:Delirium / Q000453:epidemiology / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015654:Herpesvirus 6, Human / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D019349:Roseolovirus Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D014180:Transplantation; D014775:Virus Activation / Q000502:physiology*; D055815:Young Adult